16 Jul 2018

Cortese S et al. Lancet Psychiatry 2018; 5: 717-726

A number of studies have investigated the possible link between ADHD and asthma, however the available evidence is inconclusive due to confounding factors. Awareness of a significant association, from a clinical and public health perspective, would prompt asthma specialists to refer patients with ADHD symptoms to ADHD specialists and vice versa, thereby helping reduce the delay in diagnosis that is currently a concern in both ADHD and asthma. Moreover, if there is a significant link between ADHD and asthma, this would provide more insight into the pathophysiology of ADHD, as well as the possible role of allergic mechanisms in the disorder. To determine whether a significant association exists between ADHD and asthma, this study conducted a systematic review and meta-analysis of the available data, and validated the findings using a Swedish population-based cohort study to control for all relevant confounders.

For the systematic review and meta-analysis, the authors searched PubMed, PsycINFO, Embase, Embase Classic, Ovid MEDLINE and Web of Knowledge databases for articles on the association between ADHD and asthma published up to 31 October 2017. Articles were not restricted on language, date or article type, and although observational studies allowing estimation of the ADHD–asthma association were included, studies with <10 participants per group were excluded due to low statistical power. Only studies which confirmed a clinical diagnosis of asthma* or ADHD† in children or adults were included in the analysis, regardless of previous or current treatment of ADHD. The Newcastle-Ottawa Scale was used to assess study quality and, depending on the study design, the authors of the selected articles were contacted to request unpublished data.‡ The primary outcome was the crude association between ADHD and asthma, expressed by unadjusted odds ratios (ORs).

A population-based cohort study was also conducted in individuals born between 1 January 1992 and 31 December 2006, using data from Swedish national registers. In this study, individuals with ADHD were identified as those with a clinical diagnosis based on the International Statistical Classification of Diseases and Related Health Problems (ICD)-9 (code 314) or ICD-10 (code F90) recorded in the National Patient Register before 31 December 2013. Individuals with asthma were identified as those with either a clinical diagnosis (ICD-9 code 493 or ICD-10 code J45–J46) or those who had two filled prescriptions for asthma medication in the Prescribed Drug Register. To estimate the adjusted OR for the association between ADHD and asthma, covariates from the individual studies that were classified as potential confounders§ were adjusted for.

A total of 2649 potentially eligible citations were identified, from which 49 datasets met the inclusion criteria for the meta-analysis, giving a total of 210,363 participants with ADHD and 3,115,168 without ADHD to be included in the analysis. The primary analysis showed that there was a significant association between ADHD and asthma (pooled OR 1.66, 95% confidence interval [CI] 1.22–2.26). The pooled prevalence of asthma in individuals with ADHD was 16.9% (95% CI 12.0–23.0) and 11.5% (95% CI 9.8–13.4) in those without ADHD. The pooled prevalence of ADHD in individuals with asthma was 8.8% (95% CI 6.2–12.2) and 5.6% (95% CI 4.5–7.0) in those without asthma.

In the Swedish population-based cohort study, 1,575,377 individuals were included, of whom 3.7% had ADHD and 16.5% had asthma. The prevalence of asthma was significantly higher in individuals with ADHD compared with those without (24.8% versus 16.1%; p<0.0001) and the prevalence of ADHD was significantly higher in individuals with asthma compared with those without (5.5% versus 3.3%; p<0.0001). Asthma was significantly associated with ADHD when adjusted only for gender and birth year, and this association remained significant after simultaneous adjustment for all covariates (OR 1.45, 95% CI 1.41–1.48).

This systematic review and meta-analysis had some limitations. The role of possible confounders in the association between ADHD and asthma could not be fully assessed, because most confounders were missing from several of the studies. Additionally, significant heterogeneity was found between studies, and was high in most of the analyses, suggesting that the pooled OR cannot appropriately summarise results from all datasets. However, heterogeneity decreased when adjusted ORs from clinical and population-based cross-sectional studies and studies with lifetime and current prevalence of asthma were analysed separately, suggesting that study design and temporality may have contributed to the variability of the results. In addition, the authors indicated that they found potential publication biases for some of their analyses and that the study quality ratings suggested that poor representativeness was of concern in most included studies. The Swedish population-based study also had some limitations. For instance, diagnosis of ADHD was based on ICD codes, and not on Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, therefore it is possible that only patients with more severe symptoms were defined as having ADHD in the study. Similarly, an overdiagnoses of asthma may have occurred, as both the National Patient Register and the Prescribed Drug Register were used to determine the prevalence of asthma. Finally, the study could not verify the extent to which asthma medications contribute to ADHD symptoms.

In concluding, the authors emphasised that although this study did not aim to assess the longitudinal association between ADHD and asthma, which may have provided insight into potential causative factors in this association, it did demonstrate that there is a cross-sectional association between the two disorders even after controlling for many potential confounders. These results have important clinical implications, as currently neither ADHD nor asthma clinical guidelines mention the other disorder, and awareness of this association may lead to more prompt referral of patients with asthma presenting with symptoms of ADHD to an ADHD specialist and vice versa.

*Asthma was diagnosed according to history and clinical course, spirometry (in patients aged ≥5 years old as recommended by the National Asthma Education and Prevention Program), symptom frequency, use of rescue medication or via questionnaires completed by parents or caregivers. In children aged <5 years old a spirometry often cannot be done; therefore, use of asthma medications may have helped establish diagnosis†Individuals must have been diagnosed with ADHD according to DSM-III, DSM-III-R, DSM-IV, DSM-IV-TR or DSM-5TM criteria, or hyperkinetic disorder according to the ICD-10 or previous versions. Individuals diagnosed with ADHD according to a validated ADHD rating scale or recorded in medical files or registries were also included in the analysis‡Authors were systematically contacted if the data they reported were not usable, for example, studies that collected information on the prevalence of ADHD or asthma, but did not report data from which an OR could be calculated§Covariates classified as confounders included parental-level or family-level factors such as highest parental education status and family disposable income, and individual-level factors such as gender, year of birth, birthweight, gestational age and diagnosis of eczema in childhood (as it has been suggested that the link between ADHD and asthma is accounted for by earlier eczema)

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